1. Insights into a novel nuclear function for Fascin in the regulation of the amino-acid transporter SLC3A2.
- Author
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Saad A, Bijian K, Qiu D, da Silva SD, Marques M, Chang CH, Nassour H, Ramotar D, Damaraju S, Mackey J, Bismar T, Witcher M, and Alaoui-Jamali MA
- Subjects
- Breast Neoplasms metabolism, Cell Line, Tumor, Cell Nucleus metabolism, DNA-Binding Proteins, HEK293 Cells, Histones metabolism, Humans, Nuclear Proteins metabolism, Phosphorylation, TOR Serine-Threonine Kinases metabolism, Transcriptome, Carrier Proteins metabolism, Fusion Regulatory Protein 1, Heavy Chain metabolism, Gene Expression, Gene Expression Regulation, Microfilament Proteins metabolism
- Abstract
Fascin 1 (FSCN1) is a cytoskeleton-associated protein recognized to function primarily in the regulation of cytoskeleton structure and formation of plasma membrane protrusions. Here we report a novel nuclear function for Fascin 1. Biochemical studies and genome wide localization using ChIP-seq identified phosphorylated Fascin 1 (pFascin) in complexes associated with transcription and that it co-localizes with histone H3 Lys4 trimethylation (H3K4me3) on chromatin. Gene expression profiling identified genes affected by Fascin 1 including SLC3A2, a gene encoding for a plasma membrane transporter that regulates intracellular amino acid levels. RbBP5, a subunit of the H3K4 histone methyltransferase (HMT) complex was found to interact with Fascin 1 supporting its role in H3K4me3 establishment at target genes. Moreover, we show that changes to SLC3A2 levels affect amino acid-mediated mTORC1 activation. These results reveal that Fascin 1 has a yet undiscovered nuclear function as an epigenetic modulator of genes essential for amino acid metabolism.
- Published
- 2016
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